tbuckley/cabot-search huggingface dataset:
Macrophage-derived exosomes modulate wear particle-induced osteolysis via miR-3470b targeting TAB3/NF-κB signaling
Authors: Baiqi Pan, Ziji Zhang, Xiaoyu Wu, Guoyan Xian, Xuantao Hu, Minghui Gu, Linli Zheng, Xiang Li, Lingli Long, Weishen Chen, Puyi Sheng
Journal: Bioactive Materials (2023)

Aseptic prosthesis loosening (APL) is one of the most prevalent complications associated with arthroplasty. The main cause is the periprosthetic osteolysis induced by wear particles. However, the specific mechanisms of crosstalk between immune cells and osteoclasts/osteoblasts during osteolysis are unclear. In this study, we report the role and mechanism of macrophage-derived exosomes in wear particle-induced osteolysis. The results of exosomes up-taken experiments revealed that osteoblast and mature osteoclasts capture macrophage-derived exosomes (M-Exo). Next-generation sequencing and RT-qPCR on M-Exo revealed that exosomal microRNA miR-3470b was downregulated in wear particle-induced osteolysis. The results of analysis on Luciferase reporter assays/fluorescence in situ hybridization (FISH)/immunofluorescence (IF)/immunohistochemistry (IHC) and co-culture experiments demonstrated that wear particles induced osteoclast differentiation by increasing the expression of NFatc1 via M-Exo miR-3470b targeting TAB3/ NF-κB signaling. We also illustrate that engineered exosomes enriching miR-3470b facilitated to suppressed the osteolysis; the microenvironment enriching with miR-3470b could suppress wear particle-induced osteolysis via inhibition of TAB3/ NF-κB in vivo. In summary, our findings indicate that macrophage-derived exosomes transfer to osteoclasts to induce osteolysis in wear particle-induced APL. Engineering exosomes enriching with miR-3470b might be a novel strategy for the targeting treatment of bone resorption-related diseases.
A Composite Serum Biomarker Index for the Diagnosis of Systemic Sclerosis–Associated Interstitial Lung Disease: A Multicenter, Observational Cohort Study
Authors: Adelle S. Jee, Iain Stewart, Peter Youssef, Stephen Adelstein, Donna Lai, Sheng Hua, Wendy Stevens, Susanna Proudman, Gene‐Siew Ngian, Ian N. Glaspole, Yuben P. Moodley, Jane F. Bleasel, Sacha Macansh, Mandana Nikpour, Joanne Sahhar, Tamera J. Corte
Journal: Arthritis & Rheumatology (2023)

Objective In patients with systemic sclerosis (SSc), we investigated composite serum biomarker panels for the diagnosis and risk stratification of SSc–associated interstitial lung disease (SSc‐ILD). Methods We analyzed 28 biomarkers in 640 participants: 259 patients with SSc‐ILD and 179 SSc patients without ILD (Australian Scleroderma Cohort Study), 172 patients with idiopathic pulmonary fibrosis (IPF‐controls) (Australian IPF Registry), and 30 healthy controls. A composite index was developed from biomarkers associated with ILD in multivariable analysis derived at empirical thresholds. We evaluated the performance of the index to identify ILD, and specifically SSc‐ILD, and its association with lung function, disease extent on radiography, and patient health–related quality of life in derivation and validation cohorts. Biomarkers to distinguish SSc‐ILD from IPF‐controls were identified. Results A composite biomarker index, comprising surfactant protein D (SP‐D), Ca15‐3, and intercellular adhesion molecule 1 (ICAM‐1), was strongly associated with SSc‐ILD diagnosis, independent of age, sex, smoking history, and lung function (for biomarker index score 3, pooled adjusted odds ratio was 12.72 (95% confidence interval 4.59–35.21) ( P &lt; 0.001). The composite index strengthened the performance of individual biomarkers for SSc‐ILD identification. In SSc patients, a higher index was associated with worse baseline disease severity (for biomarker index score 3 relative to biomarker index score 0, the adjusted absolute change in forced vital capacity percent predicted was −17.84% and the diffusing capacity for carbon monoxide percent predicted was −20.16%; both P &lt; 0.001). Conclusion A composite serum biomarker index, comprising SP‐D, Ca15‐3, and ICAM‐1, may improve the identification and risk stratification of ILD in SSc patients at baseline.
Oral lymphatic delivery of alpha-galactosylceramide and ovalbumin evokes anti-cancer immunization
Authors: Prashant Pandey, Seung Hyun Kim, Laxman Subedi, Khizra Mujahid, Yebon Kim, Young-Chang Cho, Jung-Hyun Shim, Ki-Taek Kim, Seung-Sik Cho, Jeong Uk Choi, Jin Woo Park
Journal: Journal of Controlled Release (2023)
Atrial Fibrillation Occurring During Acute Hospitalization: A Scientific Statement From the American Heart Association
Authors: Janice Y. Chyou, Ebrahim Barkoudah, Jonathan W. Dukes, Larry B. Goldstein, Jose A. Joglar, Anson M. Lee, Steven A. Lubitz, Keith A. Marill, Kevin B. Sneed, Megan M. Streur, Graham C. Wong, Rakesh Gopinathannair
Journal: Circulation (2023)

Acute atrial fibrillation is defined as atrial fibrillation detected in the setting of acute care or acute illness; atrial fibrillation may be detected or managed for the first time during acute hospitalization for another condition. Atrial fibrillation after cardiothoracic surgery is a distinct type of acute atrial fibrillation. Acute atrial fibrillation is associated with high risk of long-term atrial fibrillation recurrence, warranting clinical attention during acute hospitalization and over long-term follow-up. A framework of substrates and triggers can be useful for evaluating and managing acute atrial fibrillation. Acute management requires a multipronged approach with interdisciplinary care collaboration, tailoring treatments to the patient’s underlying substrate and acute condition. Key components of acute management include identification and treatment of triggers, selection and implementation of rate/rhythm control, and management of anticoagulation. Acute rate or rhythm control strategy should be individualized with consideration of the patient’s capacity to tolerate rapid rates or atrioventricular dyssynchrony, and the patient’s ability to tolerate the risk of the therapeutic strategy. Given the high risks of atrial fibrillation recurrence in patients with acute atrial fibrillation, clinical follow-up and heart rhythm monitoring are warranted. Long-term management is guided by patient substrate, with implications for intensity of heart rhythm monitoring, anticoagulation, and considerations for rhythm management strategies. Overall management of acute atrial fibrillation addresses substrates and triggers. The 3As of acute management are acute triggers, atrial fibrillation rate/rhythm management, and anticoagulation. The 2As and 2Ms of long-term management include monitoring of heart rhythm and modification of lifestyle and risk factors, in addition to considerations for atrial fibrillation rate/rhythm management and anticoagulation. Several gaps in knowledge related to acute atrial fibrillation exist and warrant future research.
Assessment of the Risk of Venous Thromboembolism in Nonhospitalized Patients With COVID-19
Authors: Margaret C. Fang, Kristi Reynolds, Grace H. Tabada, Priya A. Prasad, Sue Hee Sung, Anna L. Parks, Elisha Garcia, Cecilia Portugal, Dongjie Fan, Ashok P. Pai, Alan S. Go
Journal: JAMA Network Open (2023)

Importance Patients hospitalized with COVID-19 have higher rates of venous thromboembolism (VTE), but the risk and predictors of VTE among individuals with less severe COVID-19 managed in outpatient settings are less well understood. Objectives To assess the risk of VTE among outpatients with COVID-19 and identify independent predictors of VTE. Design, Setting, and Participants A retrospective cohort study was conducted at 2 integrated health care delivery systems in Northern and Southern California. Data for this study were obtained from the Kaiser Permanente Virtual Data Warehouse and electronic health records. Participants included nonhospitalized adults aged 18 years or older with COVID-19 diagnosed between January 1, 2020, and January 31, 2021, with follow-up through February 28, 2021. Exposures Patient demographic and clinical characteristics identified from integrated electronic health records. Main Outcomes and Measures The primary outcome was the rate per 100 person-years of diagnosed VTE, which was identified using an algorithm based on encounter diagnosis codes and natural language processing. Multivariable regression using a Fine-Gray subdistribution hazard model was used to identify variables independently associated with VTE risk. Multiple imputation was used to address missing data. Results A total of 398 530 outpatients with COVID-19 were identified. The mean (SD) age was 43.8 (15.8) years, 53.7% were women, and 54.3% were of self-reported Hispanic ethnicity. There were 292 (0.1%) VTE events identified over the follow-up period, for an overall rate of 0.26 (95% CI, 0.24-0.30) per 100 person-years. The sharpest increase in VTE risk was observed during the first 30 days after COVID-19 diagnosis (unadjusted rate, 0.58; 95% CI, 0.51-0.67 per 100 person-years vs 0.09; 95% CI, 0.08-0.11 per 100 person-years after 30 days). In multivariable models, the following variables were associated with a higher risk for VTE in the setting of nonhospitalized COVID-19: age 55 to 64 years (HR 1.85 [95% CI, 1.26-2.72]), 65 to 74 years (3.43 [95% CI, 2.18-5.39]), 75 to 84 years (5.46 [95% CI, 3.20-9.34]), greater than or equal to 85 years (6.51 [95% CI, 3.05-13.86]), male gender (1.49 [95% CI, 1.15-1.96]), prior VTE (7.49 [95% CI, 4.29-13.07]), thrombophilia (2.52 [95% CI, 1.04-6.14]), inflammatory bowel disease (2.43 [95% CI, 1.02-5.80]), body mass index 30.0-39.9 (1.57 [95% CI, 1.06-2.34]), and body mass index greater than or equal to 40.0 (3.07 [1.95-4.83]). Conclusions and Relevance In this cohort study of outpatients with COVID-19, the absolute risk of VTE was low. Several patient-level factors were associated with higher VTE risk; these findings may help identify subsets of patients with COVID-19 who may benefit from more intensive surveillance or VTE preventive strategies.
Let’s Stop Complaining That Early Childhood Assessments Do Not Predict IQ
Authors: Amy K. Connery
Journal: JAMA Pediatrics (2023)

This Viewpoint discusses the concern about the long-term predictive validity of early childhood development (ECD) assessments and how this concern reflects a misunderstanding of the constructs of ECD and intelligence, how they are assessed, and the myriad of other influences on the growth and trajectory of intellectual ability in children.
Interpreting the Evolutionary Echoes of a Protein Complex Essential for Inner-Ear Mechanosensation
Authors: Collin R Nisler, Yoshie Narui, Emily Scheib, Deepanshu Choudhary, Jacob D Bowman, Harsha Mandayam Bharathi, Vincent J Lynch, Marcos Sotomayor
Journal: Molecular Biology and Evolution (2023)

Abstract The sensory epithelium of the inner ear, found in all extant lineages of vertebrates, has been subjected to over 500 million years of evolution, resulting in the complex inner ear of modern vertebrates. Inner-ear adaptations are as diverse as the species in which they are found, and such unique anatomical variations have been well studied. However, the evolutionary details of the molecular machinery that is required for hearing are less well known. Two molecules that are essential for hearing in vertebrates are cadherin-23 and protocadherin-15, proteins whose interaction with one another acts as the focal point of force transmission when converting sound waves into electrical signals that the brain can interpret. This "tip-link" interaction exists in every lineage of vertebrates, but little is known about the structure or mechanical properties of these proteins in most non-mammalian lineages. Here, we use various techniques to characterize the evolution of this protein interaction. Results show how evolutionary sequence changes in this complex affect its biophysical properties both in simulations and experiments, with variations in interaction strength and dynamics among extant vertebrate lineages. Evolutionary simulations also characterize how the biophysical properties of the complex in turn constrain its evolution and provide a possible explanation for the increase in deafness-causing mutants observed in cadherin-23 relative to protocadherin-15. Together, these results suggest a general picture of tip-link evolution in which selection acted to modify the tip-link interface, although subsequent neutral evolution combined with varying degrees of purifying selection drove additional diversification in modern tetrapods.
Exploiting the biological effect exerted by lipid nanocapsules in non-alcoholic fatty liver disease
Authors: Inês Domingues, Cecilia Bohns Michalowski, Valentina Marotti, Wunan Zhang, Matthias Van Hul, Patrice D. Cani, Isabelle A. Leclercq, Ana Beloqui
Journal: Journal of Controlled Release (2023)

Non-alcoholic fatty liver disease (NAFLD) affects approximately 25% of the global adult population and can progress to end-stage liver disease with life-threatening complications; however, no pharmacologic therapy has been approved. Drug delivery systems such as lipid nanocapsules (LNCs) are a very versatile platform, easy to produce, and can induce the secretion of the native glucagon-like peptide 1 (GLP-1) when orally administered. GLP-1 analogs are currently being extensively studied in clinical trials in the context of NAFLD. Our nanosystem provides with increased levels of GLP-1, triggered by the nanocarrier itself, and by the plasmatic absorption of the encapsulated synthetic analog (exenatide). Our goal in this study was to demonstrate a better outcome and a greater impact on the metabolic syndrome and liver disease progression associated with NAFLD with our nanosystem than with the subcutaneous injection of the GLP-1 analog alone. To that end, we studied the effect of chronic administration (one month) of our nanocarriers in two mouse models of early NASH: a genetic model (foz/foz mice fed a high fat diet (HFD)) and a dietary model (C57BL/6J mice fed with a western diet plus fructose (WDF)). Our strategy had a positive impact in promoting the normalization of glucose homeostasis and insulin resistance in both models, mitigating the progression of the disease. In the liver, diverging results were observed between the models, with the foz/foz mice presenting a better outcome. Although a complete resolution of NASH was not achieved in either model, the oral administration of the nanosystem was more efficient at preventing the progression of the disease into more severe states than the subcutaneous injection. We thus confirmed our hypothesis that the oral administration of our formulation has a stronger effect on alleviating the metabolic syndrome associated with NAFLD than the subcutaneous injection of the peptide.
Familial <scp>Co‐Aggregation</scp> of Idiopathic Inflammatory Myopathies and Cancer: A Swedish <scp>Population‐Based</scp> Study
Authors: Weng Ian Che, Fredrik Baecklund, Karin Hellgren, Ralf Kuja‐Halkola, Ingrid E. Lundberg, Helga Westerlind, Marie Holmqvist
Journal: Arthritis & Rheumatology (2023)

To examine if idiopathic inflammatory myopathies (IIMs) share familial susceptibility with cancer, we estimated the familial co-aggregation of these diseases.This Swedish population-based family study with data from national registers included 8,460 first-degree relatives of patients with IIM and 41,127 relatives of matched individuals without IIM. We modeled the adjusted odds ratios (ORs) of familial co-aggregation of IIM and cancer using conditional logistic regressions and adjusted for sex and birth year of index individuals and their first-degree relatives. We examined the associations for cancer overall and stratified by several factors of interest. We also performed exploratory analyses for specific cancer types.We observed no statistically significant familial associations between IIM and cancer overall. However, there was a familial association in male relative pairs of patients with dermatomyositis (adjusted OR for familial association 1.39 [95% confidence interval (95% CI) 1.15-1.68]). The association remained statistically significant after controlling for multiple testing. Moreover, this finding was consistent between kinships. Familial co-aggregation of IIM and cancer diagnosed before 50 years of age was only observed in offspring. In exploratory analyses, only the familial associations for myeloid malignancies (adjusted OR 2.27 [95% CI 1.43-3.60]) and liver cancer (adjusted OR 2.01 [95% CI 1.21-3.33]) in male relative pairs remained significant after controlling for multiple testing.We found little evidence of shared familial susceptibility as a major pathologic mechanism contributing to the co-occurrence of IIM and cancer overall. There could be subsets of patients and cancer types for which familial factors including genetics and shared environments are of more importance, but these findings need replication.
Biomechanics of surgical knot security: a systematic review
Authors: Yoke-Rung Wong, Duncan A. McGrouther
Journal: International Journal of Surgery (2023)

This review aims to identify publications on quantitative biomechanical testing of surgical knot security and the physical factors that determine knot security and failure.An electronic literature search was performed in accordance with PRISMA guidelines in January 2022 utilizing the PubMed and Google Scholar databases to look for objective biomechanical studies on knot security in surgery using the primary terms 'knot security' and 'biomechanical testing'.Thirty-six articles were included. Twenty-four configurations of surface, laparoscopic, and arthroscopic knots were studied. Biomechanical tensile testing was used to evaluate knot security in vitro . Load to failure (N) and elongation at knot failure (mm) were quantified by static and cyclic testing to evaluate the knot holding capacity and failure mechanism of slippage or rupture.This review reassures that the knot configuration, suture materials, suture sizes, and number of throws are key factors in determining the knot's security. Knot configuration has to be simple for laparoscopic and arthroscopic knots due to the confined space of the operating site. With the advent of stronger suture materials for high-tension surgical reconstructive procedures, there is an unmet need to understand the physical behavior of the knot and the factors that determine its resistance to slippage or rupture.Level of Evidence: Level IV.
Adverse birth outcomes of adolescent and young adult women diagnosed with cancer during pregnancy
Authors: Andrea C Betts, L Aubree Shay, Philip J Lupo, Sandi L Pruitt, Michael E Roth, Marlyn A Allicock, Barbara A Cohn, Caitlin C Murphy
Journal: JNCI Journal of the National Cancer Institute (2023)

We examined adverse birth outcomes among adolescent and young adult women diagnosed with cancer (AYA women, ages 15-39 years) during pregnancy.
Specialty Consultation Use by Pediatric Hospitalists—A New Type of Health Care Variation
Authors: Jennifer P. Stevens
Journal: JAMA Network Open (2023)

Andrew S. Kern-Goldberger, MD, MSCE; Evan M. Dalton, MD; Irit R. Rasooly, MD, MSCE; Morgan Congdon, MD, MPH, MSEd; Deepthi Gunturi, MS; Lezhou Wu, MPH, PhD; Yun Li, PhD; Jeffrey S. Gerber, MD, PhD; Christopher P. Bonafide, MD, MSCE
Shotgun Metagenomics of Gastric Biopsies Reveals Compositional and Functional Microbiome Shifts in High- and Low-Gastric-Cancer-Risk Populations from Colombia, South America
Authors: Anthony Mannion, Alexander Sheh, Zeli Shen, JoAnn Dzink-Fox, M. Blanca Piazuelo, Keith T Wilson, Richard Peek, James G. Fox
Journal: Gut Microbes (2023)

Along with Helicobacter pylori infection, the gastric microbiota is hypothesized to modulate stomach cancer risk in susceptible individuals. Whole metagenomic shotgun sequencing (WMS) is a sequencing approach to characterize the microbiome with advantages over traditional culture and 16S rRNA sequencing including identification of bacterial and non-bacterial taxa, species/strain resolution, and functional characterization of the microbiota. In this study, we used WMS to survey the microbiome in extracted DNA from antral gastric biopsy samples from Colombian patients residing in the high-risk gastric cancer town Túquerres (n = 10, H. pylori-positive = 7) and low-risk town of Tumaco (n = 10, H. pylori-positive = 6). Kraken2/Bracken was used for taxonomic classification and abundance. Functional gene profiles were inferred by InterProScan and KEGG analysis of assembled contigs and gene annotation. The most abundant taxa represented bacteria, non-human eukaryota, and viral genera found in skin, oral, food, and plant/soil environments including Staphylococus, Streptococcus, Bacillus, Aspergillus, and Siphoviridae. H. pylori was the predominant taxa present in H. pylori-positive samples. Beta diversity was significantly different based on H. pylori-status, risk group, and sex. WMS detected more bacterial taxa than 16S rRNA sequencing and aerobic, anaerobic, and microaerobic culture performed on the same gastric biopsy samples. WMS identified significant differences in functional profiles found between H. pylori-status, but not risk or sex groups. H. pylori-positive samples were significantly enriched for H. pylori-specific genes including virulence factors such as vacA, cagA, and urease, while carbohydrate and amino acid metabolism genes were enriched in H. pylori-negative samples. This study shows WMS has the potential to characterize the taxonomy and function of the gastric microbiome as risk factors for H. pylori-associated gastric disease. Future studies will be needed to compare and validate WMS versus traditional culture and 16S rRNA sequencing approaches for characterization of the gastric microbiome.
Physical Frailty, Genetic Predisposition, and Incident Parkinson Disease
Authors: Zekun Zheng, Yanling Lv, Shuang Rong, Taoping Sun, Liangkai Chen
Journal: JAMA Neurology (2023)

Cross-sectional evidence implicates high prevalent frailty in patients with Parkinson disease (PD), whereas the longitudinal association remains unknown.
Reply
Authors: Yu‐Hsiu Chen, Xin Zhang, Virginia Byers Kraus
Journal: Arthritis & Rheumatology (2023)

Arthritis & RheumatologyVolume 75, Issue 9 p. 1679-1680 Letter Reply Yu-Hsiu Chen, Yu-Hsiu Chen orcid.org/0000-0001-8960-1758 Duke Molecular Physiology Institute, Duke University, Durham, NC, Division of Rheumatology, Immunology, and Allergy, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan and Division of Rheumatology, Immunology, and Allergy, Department of Internal Medicine, Penghu Branch, Tri-Service General Hospital, Penghu, TaiwanSearch for more papers by this authorXin Zhang, Xin Zhang orcid.org/0000-0001-7390-4439 Duke Molecular Physiology Institute Duke University and Department of Orthopaedic Surgery, Duke University School of Medicine, Durham, NCSearch for more papers by this authorVirginia Byers Kraus, Virginia Byers Kraus [email protected] Duke Molecular Physiology Institute, Duke University, Department of Orthopaedic Surgery and Department of Medicine, Duke University School of Medicine, Durham, NCSearch for more papers by this author Yu-Hsiu Chen, Yu-Hsiu Chen orcid.org/0000-0001-8960-1758 Duke Molecular Physiology Institute, Duke University, Durham, NC, Division of Rheumatology, Immunology, and Allergy, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan and Division of Rheumatology, Immunology, and Allergy, Department of Internal Medicine, Penghu Branch, Tri-Service General Hospital, Penghu, TaiwanSearch for more papers by this authorXin Zhang, Xin Zhang orcid.org/0000-0001-7390-4439 Duke Molecular Physiology Institute Duke University and Department of Orthopaedic Surgery, Duke University School of Medicine, Durham, NCSearch for more papers by this authorVirginia Byers Kraus, Virginia Byers Kraus [email protected] Duke Molecular Physiology Institute, Duke University, Department of Orthopaedic Surgery and Department of Medicine, Duke University School of Medicine, Durham, NCSearch for more papers by this author First published: 12 March 2023 https://doi.org/10.1002/art.42500